Physiology assays in human kidney organoids
Abstract
Kidney organoids derived from human pluripotent stem cells constitute a novel model of disease, development, and regenerative therapy. Organoids are human, experimentally accessible, high throughput, and enable reconstitution of tissue-scale biology in a petri dish. Although gene expression patterns in organoid cells have been analyzed extensively, less is known about the functionality of these structures. Here, we review assays of physiological function in human kidney organoids, including best practices for quality control, and future applications. Tubular structures in organoids accumulate specific molecules through active transport, including dextran and organic anions, and swell with fluid in response to cAMP stimulation. When engrafted into animal models in vivo, organoids form vascularized glomerulus-like structures capable of size-selective filtration. Organoids exhibit metabolic, endocrine, injury, and infection phenotypes, although their specificity is not yet fully clear. To properly interpret organoid physiology assays, it is important to incorporate appropriate negative and positive controls, statistical methods, data presentation, molecular mechanisms, and clinical data sets. Improvements in organoid perfusion, patterning, and maturation are needed to enable branching morphogenesis, urine production, and renal replacement. Reconstituting renal physiology with kidney organoids is a new field with potential to provide fresh insights into classical phenomena.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 01, 2022
- Source ID
- 10.1152/ajprenal.00400.2021
Entities
People
- Benjamin S Freedman
Organizations
- Allen Institute for Cell Science
- Cystinosis Research Foundation
- National Center for Advancing Translational Sciences
- National Heart, Lung, and Blood Institute
- National Institute of Diabetes and Digestive and Kidney Diseases
- Northwest Kidney Centers
- Novo Nordisk
- United States Department of Defense
- United States – Israel Binational Science Foundation
- University of Washington
- University of Washington School of Medicine